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EJ Rogers 《Canadian Metallurgical Quarterly》1976,57(10):484-486
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A new semisynthesis of human insulin starting from porcine insulin is described. NalphaA1, NalphaB1-di-Boc-desoctapeptide-(B23-30)-insulin bearing 6 free carboxyl groups is coupled with the suitably protected human insulin-(B23-30)-octapeptide. The preferred reaction site is the carboxyl group of ArgB22. Side products are eliminated by extensive chromatographic purification. 相似文献
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Creatine kinase. Modification of the working enzyme 总被引：4，自引：0，他引：4
The action of amiodarone (1.5 X 10(-5) M) on sinus node activity of spontaneously beating isolated right atria of rabbit at 30 degrees C was investigated using a microelectrode technique. The drug significantly increased the action potential duration and decreased the slope of diastolic depolarization, both effects leading to a reduction of the sinus rate. In contrast to beta-blocking agents, amiodarone reduced but did not completely abolish the adrenergic effects on the sinus node activity. It is concluded that the amiodarone-induced bradycarida observed in clinical trials might be due to a direct effect of the drug on the sinus node. 相似文献
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C Clark D Bast AM Sharp PM St Hilaire R Agha PE Stein EJ Toone RJ Read JL Brunton 《Canadian Metallurgical Quarterly》1996,19(4):891-899
The homopentameric B subunit of verotoxin 1 (VT1) binds to the glycosphingolipid receptor globotriaosylceramide (Gb3). We produced mutants with alanine substitutions for residues found near the cleft between adjacent subunits. Substitution of alanine for phenylalanine 30 (Phe-30) resulted in a fourfold reduction in B subunit binding affinity for Gb3 and a 10-fold reduction in receptor density in a solid-phase binding assay. The interaction of wild-type and mutant B subunits with Pk trisaccharide in solution was examined by titration microcalorimetry. The carbohydrate binding of the mutant was markedly impaired compared with that of the wild type and was too weak to allow calculation of a binding constant. These results demonstrate that the mutation significantly impaired the carbohydrate-binding function of the B subunit. To ensure that the mutation had not caused a significant change in structure, the mutant B subunit was crystallized and its structure was determined by X-ray diffraction. Difference Fourier analysis showed that its structure was identical to that of the wild type, except for the substitution of alanine for Phe-30. The mutation was also produced in the VT1 operon, and mutant holotoxin was purified to homogeneity. The cytotoxicity of the mutant holotoxin was reduced by a factor of 10(5) compared to that of the wild type in the Vero cell cytotoxicity assay. The results suggest that the aromatic ring of Phe-30 plays a major role in binding of the B subunit to the Galalpha1-4Galbeta1-4Glc trisaccharide portion of Gb3. Examination of the VT1 B crystal structure suggests two potential carbohydrate-binding sites which lie on either side of Phe-30. 相似文献
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We have studied the effect of sevoflurane and desflurane on the hepatic elimination of diazepam, by incubating slices of rat livers in a closed system. Protein free and protein containing (albumin 10 g litre-1) buffers were used to examine the effect of the anaesthetics on enzyme activity and diazepam binding to albumin. Both anaesthetics (in concentrations of 0.5, 1.5 and 3.0 mmol litre-1) reduced the elimination of diazepam slightly in the absence of albumin, while the presence of the protein increased elimination to a maximum of 30% at the greatest concentration of the anaesthetics. These data support previous observations that volatile anaesthetics may interact pharmacokinetically with both liver enzyme activity and drug binding to albumin. 相似文献
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Electron donating free radicals NAD(.), (.)CO2(-), MV(.)+, and e(aq)-, generated by pulse radiolysis, reduce resazurin (RNO) with rate constants of 1.9 x 10(9), 2.8 x 10(9), 4.8 x 10(9), and 2.3 x 10(10) M(-1) s(-1), respectively, neutral solution. The semireduced dye (RN(.)-O- disproportionates slowly to RN (resorufin) and RNO. There was little evidence that RN(.)-O- behaves as an oxidizing species capable of initiating chain reactions, for instance via oxidation of NADH to NAD(.). The oxidizing radicals GS(.), (.)OH, and N3(.) interact with RNO via complex consecutive processes, probably by addition-elimination reactions. Stable products generated upon oxidation of RNO by N3(.) exhibit a red-shifted absorption, but GS(.) and (.)OH also cause partial reduction to RN. Neither O2(.)- nor dopa semiquinone nor tyrosine phenoxyl radicals appear to interact with RNO. Radicals formed by reaction of (.)OH with (Gly)3 reduce RNO to RN with stoichiometry near two (gamma-radiolysis), and there is evidence (pulse radiolysis) for direct slow O-atom transfer from RNO to these species. Resazurin is highly photosensitive under anaerobic conditions in presence of H-atom donors like NADH, GSH, or dopa. Under aerobic conditions RNO becomes an efficient catalyst of red light induced photooxidation of these donors; the RN(.)-O- intermediate, formed in the photooxidative process, is apparently recycled to RNO by O2, and by other electron acceptors. Our results suggest that RNO can behave as a photoactive, free radical generating xenobiotic compound. 相似文献